Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. Synthetic tissue engineering scaffolds provide a biomimetic construct, which employ natural biological cascades to promote healing, and native tissue integration and regeneration. As the role of cell signaling and subsequent functionality in tissue engineering becomes more clear, tissue engineers are developing multifunctional bioactive scaffolds designed to accelerate the natural healing process, which simultaneously prevent pathologies that may occur post-implantation. Ideal scaffolds are capable of presenting a physiochemical biomimetic environment while biodegrading as native tissue integrates and actively promotes or prevents desirable and undesirable physiological responses respectively. Thus, the hypotheses and specific aims of the proposed research program are: Specific Aim 1 Develop processes for optimal fabrication of highly uniform micro/nano-hierarchal scaffolds of controllable geometry and bioactivity from PCL for orthopedic tissue engineering applications Specific Aim 2 Determine the effect of nanostructured surface morphology (size of nanowires) on the behavior of MSCs (adhesion, viability, morphology, differentiation, phenotype) both short term (days) and long term (several weeks) Specific Aim 3 Determine in vivo biocompatibility and oseointegration properties of micro/nano- hierarchal scaffolds Considering the limitations of the current gold-standard treatment for critical sized defects, biodegradable synthetic bone scaffolds hold a lot of promise for future treatment regimes. Therefore, synthetic bone tissue engineered scaffolds have been aggressively pursued in the last two decades, and now have emerged as a promising alternative to conventional therapies for repairing bone defects. The fundamental concept behind tissue engineering is to utilize the body's natural biological response to tissue damage in conjunction with engineering principles. Successful synthetic bone scaffolds promotes progenitor cell migration on to the scaffold (osteoconduction), support or induce osteogenic differentiation (osteoinduction), and finally integrate with host tissue (osseointegration). Additional critical aspects of successful bone scaffolds include biocompatibility, temporary mechanical stability, biodegradability, porosity, and controlled release of bioactive molecules to accelerate healing and/or prevent undesired pathologies. This proposed project outlines the motivation and reasoning behind the development of the PCL nanowire surfaces. PUBLIC HEALTH RELEVANCE: Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. This proposed project outlines the motivation and reasoning behind the development of the polymeric nanowire surfaces as a bone graft material.